Abstract
Neurons typically form daisy chains of synaptic connections with other neurons, but they can also form synapses with themselves. Although such self-synapses, or autapses, are comparatively rare in vivo, they are surprisingly common in dissociated neuronal cultures. At first glance, autapses in culture seem like a mere curiosity. However, by providing a simple model system in which a single recording electrode gives simultaneous access to the pre- and postsynaptic compartments, autaptic cultures have proven to be invaluable in facilitating important and elegant experiments in the area of synaptic neuroscience. Here, I provide detailed protocols for preparing and recording from autaptic cultures (also called micro-island or microdot cultures). Variations on the basic procedure are presented, as well as practical tips for optimizing the outcomes. I also illustrate the utility of autaptic cultures by reviewing the types of experiments that have used them over the past three decades. These examples serve to highlight the power and elegance of this simple model system, and will hopefully inspire new experiments for the interrogation of synaptic function.
Highlights
The brain achieves its astonishing feats of information processing in part because of the complexity of its synaptic connections
These experiments have shown, for example, how transporters in the glia modulate the timecourse of the autaptic EPSC in the neuron (Mennerick and Zorumski, 1995b; Mennerick et al, 1999), and how autaptic neurons grown without glial contact exhibit more asynchronous neurotransmitter release (Sobieski et al, 2015)
Despite a current tendency to study complex and preferably in vivo neural networks, autaptic cultures still have an important place in the toolbox of cellular neuroscientists because they enable straightforward, elegant experiments that address fundamental questions about synaptic transmission
Summary
The brain achieves its astonishing feats of information processing in part because of the complexity of its synaptic connections. The term ‘‘autapse’’ entered the neuroscience lexicon only in 1972 when it was first coined to describe putative self-synapses on Golgi-stained pyramidal neurons in rabbit neocortex (Van der Loos and Glaser, 1972) Since both anatomical and physiological evidence for autapses in vivo has accumulated steadily (Karabelas and Purpura, 1980; Park et al, 1980; Peters and Proskauer, 1980; Preston et al, 1980; Lübke et al, 1996; Cobb et al, 1997; Tamás et al, 1997; Pouzat and Marty, 1998, 1999; Pawelzik et al, 2003; Bacci and Huguenard, 2006; Connelly and Lees, 2010; Manseau et al, 2010; Jiang et al, 2012, 2015; Yin et al, 2018; Deleuze et al, 2019). The importance of autapses for the normal operation of neural circuits remains a matter for speculation (Bekkers, 1998, 2003, 2009; White et al, 1998; Li et al, 2010; Connelly, 2014; Deleuze et al, 2014; Guo et al, 2016; Wiles et al, 2017)
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